Use of Bromhexine in the Management of Respiratory Diseases in Chickens
DOI: Views 639 Downloads 0
Many respiratory diseases of chickens undergo airway contraction from edema, the formation of mucus, and cellular penetration. Based on the natural breath by breath system sometimes the normal amount of air may not flow easily. So the airways may vulnerable to failure. That leads to the common symptoms of the disease such as noisy breathing, cough, lethargy, and sneeze. Therefore, mucolytic drug therapy (bromhexine) is one of the options to increase the diameter of the airway that may mitigate or even eliminate these clinical signs. Hence the objective of this study is to review the literature regarding the use of bromhexine for the prevention and treatment of respiratory diseases.
Respiratory diseases, chickens, mucus, disease symptoms, bromhexine.
Ali, Q., Mafeng, L., Anchun, C., 2019. Use of Bromhexine in the Management of Respiratory Diseases in Chickens. PSM Microbiol., 4(4): 83-87.
Within the increasing population of the world the demand for poultry protein is increasing day by day (Butt et al., 2016; Hadyait et al., 2018). Respiratory infections in poultry are the major group of diseases that cause significant economic losses to the poultry industry (Baksi et al., 2017). Now a day the tremendous growth of the poultry industry makes it more susceptible to respiratory diseases (Ashraf et al., 2019). So different chemical compounds in form of veterinary drugs with the object of preventing and treating animals including poultry birds from respiratory diseases have been used (Davidson et al., 2008; Sumano and Gutierrez, 2008).
Self-defense mechanism against viruses and bacteria
In response to airborne disease agents, the poultry respiratory tract acts as a self-immune defense. There are three defensive mechanisms (cilia, mucus secretions, and scavenging cells) that protect poultry respiratory health. Cilia are hair-like structures in the trachea of poultry birds that are engaged in pushing the trapped particles. There are some goblet cells in the trachea that produce mucus. Mucus is composed of 95% water and 2% glycoprotein that is enriched in sialic acid (Cottel, 1995). The uniformity of the production of mucus in the trachea is vital for the better activity of cilia. At the submucosal level, the goblet cells produce more components of fluids along with a lesser concentration of glycoprotein (Bartoll, 2002). It has also been observed that the production of more viscosity of the mucus is due to bacterial or viral infection. Actually, in a common cold environment the rhinovirus, coronavirus, and adenovirus cause infection in the upper respiratory tract (Schellack and Labuschagne, 2014). And that the virus damages the ciliated cells that lead to the release of inflammatory mediators that causes the inflammation of linings of nasal tissues. Along with the increased permeability of capillary cell walls undergoes edema. Whereas the edema is responsible for coughing, sneezing, fever, sore throat, and congestion (Schellack and Labuschagne, 2014: National Prescribing Centre, 2017). But in recent studies, it has been known that bromhexine acts as an antioxidant and anti-inflammatory agent (Gibbs et al., 1999) against rhinovirus, coronavirus, adenovirus, and many other bacteria. Whereas the scavenging cells in the lungs engulf the bacteria and inhaled particles. The air within unnecessary dusting produces the tracheal plugs that are unfavorable for the health of chickens. It has been noted that the production of ammonia from 10 to 40 ppm increased the excessive mucus that damage the cilia (Jacob and Pescatore, 2017).
Introduction of Bromhexine
To get rid of these respiratory diseases different mucolytic agents (bromhexine and ambroxol) are used in poultry farming. These bromhexine and ambroxol medicinal products were first time registered in European Union Member State in 1963 and 1978 respectively and recently used in European Union Member State (Debuf, 1991). Along with these mucolytic drugs (bromhexine, ambroxol, carbocysteine, and ethylenediamine) are abundantly used in poultry farming (Lizbeth et al., 2016).
Bromhexine is a kind of cough related medicine having structural formula Br-CH2-CH2-CH2-CH2-CH2-CH3 (NCBI, 2019). Bromhexine and its metabolites such as ambroxol and cyclohexanol hydrochloride have been abundantly used in the poultry industry because of their mucolytic characteristics in the treatment of respiratory-related problems such as cystic fibrosis and chronic obstructive airway disease (Mestorino et al., 2011). The mucolytic drugs are mostly used with the antibiotics for the treatment of respiratory diseases to increase the elimination of excessive persistent mucus (Debuf, 1991; Bottje et al., 1998). So that the low viscosity mucus can easily be removed during coughing. Whereas Garst et al. (1991) stated that it is used to produce natural chemicals that are engaged in the manufacturing of Bromo-cyclic compounds. It is always preferable to use the drugs within the water. As the birds drink water at that time when the birds do not eat (Debuf, 1991). The advantage of the use of waterborne drugs is that these reduce the spread of disease by the contamination of water with the drugs (Clubb, 1984).
Absorption and the action mechanism of bromhexine in poultry
Oral supplementation of bromhexine is absorbed in the GIT (gastrointestinal tract) and it’s wide metabolism is started in the liver. Just within one hour about 20% bromhexine from the liver is disseminated into the body tissues and attached to the plasma proteins (Reynolds, 2002). Whereas in lungs the bromhexine destroys the composition of acid mucopolysaccharide fibers and remove the mucus (thick liquid) by converting it into less thick liquid from the lungs. The remaining dose of about 85% to 90% bromhexine is removed through the urine (Lund, 1994; Morton et al., 1999). However, the mechanism of action of bromhexine has been moderately investigated. Some of its actions have been examined that control the production of mucosubstances, sputum quality, and quantity, ciliary activity, diffusion of antibiotics and brutality, and regularity of cough. These characteristics discriminate it from other diseases (Alessandro et al., 2017).
Effect of bromhexine on the antibiotic penetration
Bromhexine can be used for the cure of respiratory diseases in amalgamation with antimicrobial agents. It destroys the mucopolysaccharides of bronchial secretion and enhances the saturation of antimicrobial drugs (Mestorino et al., 2011). These agents are currently used as a therapy for the destruction of pathogens. For example, in the case of alcoholic chronic pancreatitis where the viscosity of pancreatic juice is increased (Tscimoto et al., 2004). Furthermore, bromhexine HCl increases the bronchial dissemination of antimicrobial drugs and thus interrupt the mucopolysaccharides of the bronchial secretions (Bergogne et al., 1985). It has been described that the bromhexine hydrochloride enhanced the concentration of oxytetracycline in the secreted mucus (Bergogne, 1985; Martin et al., 1993) and that it also starts the reverse reaction of mucolytic activity of oxytetracycline in vivo (Martin et al., 1993). So it is possible to assume that bromhexine is a mucolytic agent that introduces changes in the tracheobronchial secretions. However further work on bromhexine is required for the treatment of respiratory diseases in poultry birds.
Although from previous studies the practical facts related to the poultry field indicate only reticent and positive results, it is not denotable that the efficiency of bromhexine is arguable. Bromhexine within a very minute occurrence of placid side effects is associated with positive perfection in the clearance of mucus from respiratory disease birds. There are inadequate facts in the literature to sustain the use of bromhexine for the prevention and treatment of these respiratory diseases. Bromhexine is currently used as a medicinal therapy for the removal of mucus produced by the infection of bacterial and viral pathogens.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
Alessandro, Z., Massimiliano, M., Ahmad, K., 2017. A reappraisal of the mucoactive activity and clinical efficacy of bromhexine. Multidiscip, Respir, Med., 12: 7.
Ashraf, A., Iqbal, I., Iqbal, M.N., 2019. Waterborne Diseases in Poultry: Drinking Water as a Risk Factor to Poultry Health. PSM Microbiol., 4(3): 75-79.
Baksi, S., Rao, N., Chauhan, P., 2017. Seroprevalence of Ornithobacterium rhinotracheale in broiler breeders in India. PSM Vet. Res., 2(2): 29-32.
Bartoll, P., 2002. Factores que afectan la integridad de la mucosa nasal. Chapter 16. Farm. Hosp., 1273-1274.
Bergogne, B., Berthelot, G., Kafe, H.P., Doournovo, P., 1985. Influence of a fluidifying agent (bromhexine) on the penetration of antibiotics into respiratory secretions. Int. J. Clin. Pharmacol. Res., 5(3): 341-344.
Bottje, W.G., Wangs, S., Kelly, F.J., Dunster, C., Willians, A., Mudway, I., 1998. Antioxidant defenses in lung lining fluid of brilers; impact of poor ventilation conditions. Poult. Sci., 77: 516-522.
Butt, N.S., Ashraf, A., Alam, S., Iqbal, M.N., Irfan, M., Fadlalla, M.H.M., Ijaz, S., 2016. Estimation of Iron in Liver, Gizzard, Breast and Thigh Muscles of Broiler Chicken. PSM Vet. Res., 01(2): 54-59.
Clubb, S.L., 1984. Therapeutics in avian medicine. The Veterinary clinics of North America. 14: 345-361.
Cottel, G.P., Surkin, H.B., 1995. Pharmacology for respiratory care practitioners. Drugs affecting the respiratory system mucokinetic, surface-active and antitussive agents. 15: 201–218.
Davidson, F., Kaspers, B., Schat, A.K., 2008. Avian Inmunology; First Edition. 273-284.
Debuf, Y., 1991. The veterinary formulary. Handbook of medicines used in veterinary practice. The Pharmaceutical Press, London. 448.
Garst, J., Ungvary, F., Batlaw, R., Lawrence, K., 1991. Solvent attack in Grignard reagent formation from bromocyclopropane and 1-bromohexane in diethyl ether. J. Ameri. Chemi. Soc., 113(14): 5392-5397.
Gibbs, B.F., Scmutzler, W., Vollrath, I.B., Brosthardt, P., Braam, U., Wolff, H.H., Zwadlo-Klarwasser, G., 1999. Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells. Inflamation Res., 48: 86-93.
Hadyait, M.A., Qayyum, A., Bhatti, E.M., Salim, S., Ali, A., Shahzadi, M., 2018. Estimation of Heavy Metals in Liver, Gizzard, Breast and Thigh Muscles of Broiler Chicken in Different Area of Lahore by ICP-OES. PSM Vet. Res., 3(1): 10-14.
Jacob, J., Pescatore, A., 2017. Glucans and the Poultry Immune System. Am. J. Immunol., 13(1): 45-49.
Martin, G.P., Loveday, B.E., Mariot, C., 1993. Bromhexine plus oxytetracycline: the effect of combined administration upon the rheological properties of mucus from the mini-pig. J. Pharm. Pharmacol., 45(2): 126-30.
Morton, I., Morton, I., Hall, J., 1999. Concise dictionary of pharmacological agents. Pp. 55. 0-7514-0499 3.
Lizbeth, C., Hector, S., Luis, M., Graciela, T.T., Lilia, G., 2016. Rheological study of healthy chicken’s pooled tracheobronchial secretions and its modification by mucolytics drugs. Poult. Sci., 95: 2667-2672.
Lund, W., 1994. Pharmaceutical codex, London. The Pharmaceutical Press. Pp. 1117.
Mestorino, N., Marchetti, M.L., Huber, B., Errecalde Cátedra de Farmacología, J.O., 2011. Effects of bromhexine on the penetration of enrofloxacin into bronchial secretions of chicken.
National Prescribing Centre, 2017. [online] Available at: NHS National Prescribing Centre. Common cold. NHS [homepage on the Internet]. 2006.
NCBI, 2019. National Center for Biotechnology Information. PubChem Database. 1-Bromohexane,CID=8101, https://pubchem. ncbi.nlm.nih.gov/compound/1-Bromo-hexane (accessed on November 13, 2019).
Reynolds, J.E.F., 2002. The extra pharmacopoeia, London. The Pharmaceutical Press. Pp. 2483.
Schellack, N., Labuschagne, Q., 2014. Overview and management of colds and flu. Sout. Afri. Pharm. J., 81(6): 19-26.
Sumano, L.H., Gutierrez, O.L., 2008. Farmacolog ´Cl´ nica en aves comerciales. 663–671. Tscimoto, T., Takano, M., Tsurano, T., Hoppo, K., Matsumura, Y., Yamao, J., Kuriyama, S., Fukui, H., 2004. Mediatinal pancreatic pseudocyt caused by obstruction of the pancreatic duct was eliminated by bromhexine hydrochloride. Intern. Med., 43(11): 1034-8.